Genital herpes, though not officially recognized as a disease until 1966, is currently an epidemic veneral disease. About five million Americans suffer from this problem, with an estimated one-half million individuals becoming infected each year. Although many forms of forms of therapy have been tested, none has proven profoundly beneficial in decreasing the severity and frequency of the clinical manifestations. Once established, herpes virus particles retreat into the nerve trunk and remain latent in the asymptomatic period. They are inaccessible to therapy in their ganglionic home. Therefore, control of herpes labialis rests on the ability we have to suppress symptoms promptly as the virus begins to re- express itself. It appears this could best be done by delivering an effective antiviral agent into the living epidermal tissues of the skin during the prodromal stage of lesion development. Interferon seems to have especially high potential for the treatment of herpes, condylomata acuminata and other similarly manifested disease states. However, systemic regimens adequate to suppress skin symptomology often results in adverse systemic effects and still may not overcome the inaccessibility of the target tissue to the drug. "Drug delivery" remains the singularly most limiting factor to the effective treatment of herpes. Liposomes recently have received much attention in the search for a more effective means of delivering intrinsically active drugs to their tissue targets. Recent studies in our laboratories and others have shown that large amounts of interferon are taken up by liposomes, that significant amounts of this interferon are internalized within the liposome, that liposomally entrapped interferon is stable for at least one year, and that interferon maintains its antiviral activity under these conditions. In recent studies, we have shown that liposomes facilitate skin deposition of drugs and that when interferon is encapsulated in a liposome by a technique which facilitates its association with bilayers, the polypeptide penetrates intact skin and is therapeutically active; however, interferon incorporated in traditional vehicles lack therapeutic efficacy. The goal of these studies is to continue to assess the possibility of treating virus-infected epithelial cells with liposomally entrapped interferon delivered by the transdermal route. Specifically, we wish to isolate and elucidate the factors related to the liposomal entrapment of biologically active interferon and with its subsequent delivery through intact skin to tissue infected by virus. Since interferon's biological activity is long-lasting when in liposomes, liposomes also appear to offer a practical as well as an effective means of delivery of interferon to lesion sits. Furthermore, a systematic analysis of the parameters involved may provide a rational hypothesis and guidance for future research on the topical delivery of other liposomally entrapped drugs for the treatment of other disease states.